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Protein

Thymidine phosphorylase

Gene

TYMP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

May have a role in maintaining the integrity of the blood vessels. Has growth promoting activity on endothelial cells, angiogenic activity in vivo and chemotactic activity on endothelial cells in vitro.1 Publication
Catalyzes the reversible phosphorolysis of thymidine. The produced molecules are then utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis.1 Publication

Catalytic activityi

Thymidine + phosphate = thymine + 2-deoxy-alpha-D-ribose 1-phosphate.

Pathwayi: dTMP biosynthesis via salvage pathway

This protein is involved in step 1 of the subpathway that synthesizes dTMP from thymine.
Proteins known to be involved in the 2 steps of the subpathway in this organism are:
  1. Thymidine phosphorylase, Thymidine phosphorylase (TYMP), Thymidine phosphorylase (TYMP)
  2. no protein annotated in this organism
This subpathway is part of the pathway dTMP biosynthesis via salvage pathway, which is itself part of Pyrimidine metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes dTMP from thymine, the pathway dTMP biosynthesis via salvage pathway and in Pyrimidine metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei116Substrate1
Binding sitei202Substrate1
Binding sitei217Substrate1
Binding sitei221Substrate1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Glycosyltransferase, Growth factor, Transferase

Keywords - Biological processi

Angiogenesis, Chemotaxis, Differentiation

Enzyme and pathway databases

BioCyciMetaCyc:HS00442-MONOMER.
ZFISH:HS00442-MONOMER.
BRENDAi2.4.2.4. 2681.
ReactomeiR-HSA-73614. Pyrimidine salvage reactions.
R-HSA-73621. Pyrimidine catabolism.
SABIO-RKP19971.
UniPathwayiUPA00578; UER00638.

Names & Taxonomyi

Protein namesi
Recommended name:
Thymidine phosphorylase (EC:2.4.2.4)
Short name:
TP
Alternative name(s):
Gliostatin
Platelet-derived endothelial cell growth factor
Short name:
PD-ECGF
TdRPase
Gene namesi
Name:TYMP
Synonyms:ECGF1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

HGNCiHGNC:3148. TYMP.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Involvement in diseasei

Mitochondrial DNA depletion syndrome 1, MNGIE type (MTDPS1)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA multisystem disease associated with mitochondrial dysfunction. It is clinically characterized by onset between the second and fifth decades of life, ptosis, progressive external ophthalmoplegia, gastrointestinal dysmotility (often pseudoobstruction), diffuse leukoencephalopathy, cachexia, peripheral neuropathy, and myopathy.
See also OMIM:603041
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01677744R → Q in MTDPS1. 1 PublicationCorresponds to variant rs28931613dbSNPEnsembl.1
Natural variantiVAR_007643145G → R in MTDPS1. 1 PublicationCorresponds to variant rs121913037dbSNPEnsembl.1
Natural variantiVAR_007644153G → S in MTDPS1. 1 PublicationCorresponds to variant rs121913038dbSNPEnsembl.1
Natural variantiVAR_007645222K → R in MTDPS1. 1 PublicationCorresponds to variant rs149977726dbSNPEnsembl.1
Natural variantiVAR_007646289E → A in MTDPS1. 1 PublicationCorresponds to variant rs121913036dbSNPEnsembl.1
Natural variantiVAR_007647397 – 398Missing in MTDPS1. 1 Publication2

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi199Y → A: Abolishes catalytic activity. 1 Publication1
Mutagenesisi199Y → F: Reduced catalytic activity. 1 Publication1
Mutagenesisi199Y → L: Reduced catalytic activity. 1 Publication1

Keywords - Diseasei

Disease mutation, Progressive external ophthalmoplegia

Organism-specific databases

DisGeNETi1890.
MalaCardsiTYMP.
MIMi603041. phenotype.
OpenTargetsiENSG00000025708.
Orphaneti298. Mitochondrial neurogastrointestinal encephalomyopathy.
PharmGKBiPA162407502.

Chemistry databases

ChEMBLiCHEMBL3106.
DrugBankiDB01101. Capecitabine.
DB00369. Cidofovir.
DB00322. Floxuridine.
DB00544. Fluorouracil.
DB00432. Trifluridine.

Polymorphism and mutation databases

BioMutaiTYMP.
DMDMi67477361.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PropeptideiPRO_00000358741 – 1010
ChainiPRO_000003587511 – 482Thymidine phosphorylaseAdd BLAST472

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei6PhosphothreonineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP19971.
PaxDbiP19971.
PeptideAtlasiP19971.
PRIDEiP19971.

2D gel databases

OGPiP19971.

PTM databases

iPTMnetiP19971.
PhosphoSitePlusiP19971.
SwissPalmiP19971.

Expressioni

Gene expression databases

BgeeiENSG00000025708.
CleanExiHS_TYMP.
ExpressionAtlasiP19971. baseline and differential.
GenevisibleiP19971. HS.

Organism-specific databases

HPAiCAB002518.
HPA000530.
HPA001072.

Interactioni

Subunit structurei

Homodimer.3 Publications

Protein-protein interaction databases

BioGridi108219. 21 interactors.
IntActiP19971. 1 interactor.
STRINGi9606.ENSP00000252029.

Chemistry databases

BindingDBiP19971.

Structurei

Secondary structure

1482
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi36 – 44Combined sources9
Helixi51 – 63Combined sources13
Helixi68 – 81Combined sources14
Helixi85 – 96Combined sources12
Helixi106 – 111Combined sources6
Beta strandi112 – 118Combined sources7
Helixi125 – 134Combined sources10
Turni135 – 137Combined sources3
Beta strandi139 – 143Combined sources5
Helixi154 – 158Combined sources5
Helixi170 – 180Combined sources11
Beta strandi181 – 185Combined sources5
Beta strandi189 – 192Combined sources4
Helixi193 – 204Combined sources12
Helixi211 – 224Combined sources14
Beta strandi228 – 236Combined sources9
Beta strandi240 – 244Combined sources5
Helixi245 – 261Combined sources17
Beta strandi266 – 272Combined sources7
Beta strandi280 – 283Combined sources4
Helixi284 – 294Combined sources11
Helixi300 – 316Combined sources17
Beta strandi319 – 322Combined sources4
Helixi323 – 335Combined sources13
Helixi338 – 349Combined sources12
Helixi354 – 362Combined sources9
Helixi365 – 371Combined sources7
Beta strandi376 – 382Combined sources7
Beta strandi387 – 392Combined sources6
Helixi394 – 405Combined sources12
Beta strandi409 – 412Combined sources4
Beta strandi420 – 423Combined sources4
Beta strandi436 – 446Combined sources11
Helixi449 – 458Combined sources10
Beta strandi459 – 464Combined sources6
Beta strandi475 – 477Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1UOUX-ray2.11A12-482[»]
2J0FX-ray2.31A/B/C/D1-482[»]
2WK5X-ray2.99A/B/C/D1-482[»]
2WK6X-ray2.50A/B1-482[»]
ProteinModelPortaliP19971.
SMRiP19971.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP19971.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati265 – 279R-V-A-A-A-L-X(5,6)-L-G-RAdd BLAST15
Repeati329 – 342R-V-A-A-A-L-X(5,6)-L-G-RAdd BLAST14
Repeati393 – 401R-A-L-X-X-A-L-V-L9
Repeati453 – 461R-A-L-X-X-A-L-V-L9

Sequence similaritiesi

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410IIV8. Eukaryota.
COG0213. LUCA.
GeneTreeiENSGT00390000009250.
HOGENOMiHOG000047313.
HOVERGENiHBG000082.
InParanoidiP19971.
KOiK00758.
OMAiEVGCCIV.
OrthoDBiEOG091G08UG.
PhylomeDBiP19971.
TreeFamiTF332198.

Family and domain databases

Gene3Di3.40.1030.10. 1 hit.
3.90.1170.30. 1 hit.
InterProiIPR000312. Glycosyl_Trfase_fam3.
IPR017459. Glycosyl_Trfase_fam3_N_dom.
IPR013102. PYNP_C.
IPR018090. Pyrmidine_PPas_bac/euk.
IPR017872. Pyrmidine_PPase_CS.
IPR000053. Thymidine/pyrmidine_PPase.
[Graphical view]
PANTHERiPTHR10515. PTHR10515. 1 hit.
PfamiPF02885. Glycos_trans_3N. 1 hit.
PF00591. Glycos_transf_3. 1 hit.
PF07831. PYNP_C. 1 hit.
[Graphical view]
PIRSFiPIRSF000478. TP_PyNP. 1 hit.
SMARTiSM00941. PYNP_C. 1 hit.
[Graphical view]
SUPFAMiSSF47648. SSF47648. 1 hit.
SSF52418. SSF52418. 1 hit.
SSF54680. SSF54680. 1 hit.
TIGRFAMsiTIGR02644. Y_phosphoryl. 1 hit.
PROSITEiPS00647. THYMID_PHOSPHORYLASE. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P19971-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAALMTPGTG APPAPGDFSG EGSQGLPDPS PEPKQLPELI RMKRDGGRLS
60 70 80 90 100
EADIRGFVAA VVNGSAQGAQ IGAMLMAIRL RGMDLEETSV LTQALAQSGQ
110 120 130 140 150
QLEWPEAWRQ QLVDKHSTGG VGDKVSLVLA PALAACGCKV PMISGRGLGH
160 170 180 190 200
TGGTLDKLES IPGFNVIQSP EQMQVLLDQA GCCIVGQSEQ LVPADGILYA
210 220 230 240 250
ARDVTATVDS LPLITASILS KKLVEGLSAL VVDVKFGGAA VFPNQEQARE
260 270 280 290 300
LAKTLVGVGA SLGLRVAAAL TAMDKPLGRC VGHALEVEEA LLCMDGAGPP
310 320 330 340 350
DLRDLVTTLG GALLWLSGHA GTQAQGAARV AAALDDGSAL GRFERMLAAQ
360 370 380 390 400
GVDPGLARAL CSGSPAERRQ LLPRAREQEE LLAPADGTVE LVRALPLALV
410 420 430 440 450
LHELGAGRSR AGEPLRLGVG AELLVDVGQR LRRGTPWLRV HRDGPALSGP
460 470 480
QSRALQEALV LSDRAPFAAP SPFAELVLPP QQ
Length:482
Mass (Da):49,955
Last modified:June 7, 2005 - v2
Checksum:i0652FA0B8F3BDE28
GO
Isoform 2 (identifier: P19971-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     386-386: D → DAPLPA

Note: No experimental confirmation available.
Show »
Length:487
Mass (Da):50,405
Checksum:iC2F16246C51DCE00
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti195D → E in AAH18160 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01677744R → Q in MTDPS1. 1 PublicationCorresponds to variant rs28931613dbSNPEnsembl.1
Natural variantiVAR_007643145G → R in MTDPS1. 1 PublicationCorresponds to variant rs121913037dbSNPEnsembl.1
Natural variantiVAR_007644153G → S in MTDPS1. 1 PublicationCorresponds to variant rs121913038dbSNPEnsembl.1
Natural variantiVAR_007645222K → R in MTDPS1. 1 PublicationCorresponds to variant rs149977726dbSNPEnsembl.1
Natural variantiVAR_007646289E → A in MTDPS1. 1 PublicationCorresponds to variant rs121913036dbSNPEnsembl.1
Natural variantiVAR_007647397 – 398Missing in MTDPS1. 1 Publication2
Natural variantiVAR_007648471S → L.2 PublicationsCorresponds to variant rs11479dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_045556386D → DAPLPA in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M63193 mRNA. Translation: AAA60043.1.
AK225269 mRNA. No translation available.
U62317 Genomic DNA. Translation: AAB03344.2.
BC018160 mRNA. Translation: AAH18160.1.
BC052211 mRNA. Translation: AAH52211.1.
CCDSiCCDS14096.1. [P19971-1]
CCDS58811.1. [P19971-2]
PIRiS03904.
RefSeqiNP_001107227.1. NM_001113755.2. [P19971-1]
NP_001107228.1. NM_001113756.2. [P19971-1]
NP_001244917.1. NM_001257988.1. [P19971-1]
NP_001244918.1. NM_001257989.1. [P19971-2]
NP_001944.1. NM_001953.4. [P19971-1]
UniGeneiHs.180903.
Hs.730607.

Genome annotation databases

EnsembliENST00000252029; ENSP00000252029; ENSG00000025708. [P19971-1]
ENST00000395678; ENSP00000379036; ENSG00000025708. [P19971-1]
ENST00000395680; ENSP00000379037; ENSG00000025708. [P19971-1]
ENST00000395681; ENSP00000379038; ENSG00000025708. [P19971-2]
GeneIDi1890.
KEGGihsa:1890.
UCSCiuc003bmb.7. human. [P19971-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M63193 mRNA. Translation: AAA60043.1.
AK225269 mRNA. No translation available.
U62317 Genomic DNA. Translation: AAB03344.2.
BC018160 mRNA. Translation: AAH18160.1.
BC052211 mRNA. Translation: AAH52211.1.
CCDSiCCDS14096.1. [P19971-1]
CCDS58811.1. [P19971-2]
PIRiS03904.
RefSeqiNP_001107227.1. NM_001113755.2. [P19971-1]
NP_001107228.1. NM_001113756.2. [P19971-1]
NP_001244917.1. NM_001257988.1. [P19971-1]
NP_001244918.1. NM_001257989.1. [P19971-2]
NP_001944.1. NM_001953.4. [P19971-1]
UniGeneiHs.180903.
Hs.730607.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1UOUX-ray2.11A12-482[»]
2J0FX-ray2.31A/B/C/D1-482[»]
2WK5X-ray2.99A/B/C/D1-482[»]
2WK6X-ray2.50A/B1-482[»]
ProteinModelPortaliP19971.
SMRiP19971.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108219. 21 interactors.
IntActiP19971. 1 interactor.
STRINGi9606.ENSP00000252029.

Chemistry databases

BindingDBiP19971.
ChEMBLiCHEMBL3106.
DrugBankiDB01101. Capecitabine.
DB00369. Cidofovir.
DB00322. Floxuridine.
DB00544. Fluorouracil.
DB00432. Trifluridine.

PTM databases

iPTMnetiP19971.
PhosphoSitePlusiP19971.
SwissPalmiP19971.

Polymorphism and mutation databases

BioMutaiTYMP.
DMDMi67477361.

2D gel databases

OGPiP19971.

Proteomic databases

MaxQBiP19971.
PaxDbiP19971.
PeptideAtlasiP19971.
PRIDEiP19971.

Protocols and materials databases

DNASUi1890.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000252029; ENSP00000252029; ENSG00000025708. [P19971-1]
ENST00000395678; ENSP00000379036; ENSG00000025708. [P19971-1]
ENST00000395680; ENSP00000379037; ENSG00000025708. [P19971-1]
ENST00000395681; ENSP00000379038; ENSG00000025708. [P19971-2]
GeneIDi1890.
KEGGihsa:1890.
UCSCiuc003bmb.7. human. [P19971-1]

Organism-specific databases

CTDi1890.
DisGeNETi1890.
GeneCardsiTYMP.
GeneReviewsiTYMP.
HGNCiHGNC:3148. TYMP.
HPAiCAB002518.
HPA000530.
HPA001072.
MalaCardsiTYMP.
MIMi131222. gene.
603041. phenotype.
neXtProtiNX_P19971.
OpenTargetsiENSG00000025708.
Orphaneti298. Mitochondrial neurogastrointestinal encephalomyopathy.
PharmGKBiPA162407502.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IIV8. Eukaryota.
COG0213. LUCA.
GeneTreeiENSGT00390000009250.
HOGENOMiHOG000047313.
HOVERGENiHBG000082.
InParanoidiP19971.
KOiK00758.
OMAiEVGCCIV.
OrthoDBiEOG091G08UG.
PhylomeDBiP19971.
TreeFamiTF332198.

Enzyme and pathway databases

UniPathwayiUPA00578; UER00638.
BioCyciMetaCyc:HS00442-MONOMER.
ZFISH:HS00442-MONOMER.
BRENDAi2.4.2.4. 2681.
ReactomeiR-HSA-73614. Pyrimidine salvage reactions.
R-HSA-73621. Pyrimidine catabolism.
SABIO-RKP19971.

Miscellaneous databases

EvolutionaryTraceiP19971.
GeneWikiiECGF1.
GenomeRNAii1890.
PROiP19971.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000025708.
CleanExiHS_TYMP.
ExpressionAtlasiP19971. baseline and differential.
GenevisibleiP19971. HS.

Family and domain databases

Gene3Di3.40.1030.10. 1 hit.
3.90.1170.30. 1 hit.
InterProiIPR000312. Glycosyl_Trfase_fam3.
IPR017459. Glycosyl_Trfase_fam3_N_dom.
IPR013102. PYNP_C.
IPR018090. Pyrmidine_PPas_bac/euk.
IPR017872. Pyrmidine_PPase_CS.
IPR000053. Thymidine/pyrmidine_PPase.
[Graphical view]
PANTHERiPTHR10515. PTHR10515. 1 hit.
PfamiPF02885. Glycos_trans_3N. 1 hit.
PF00591. Glycos_transf_3. 1 hit.
PF07831. PYNP_C. 1 hit.
[Graphical view]
PIRSFiPIRSF000478. TP_PyNP. 1 hit.
SMARTiSM00941. PYNP_C. 1 hit.
[Graphical view]
SUPFAMiSSF47648. SSF47648. 1 hit.
SSF52418. SSF52418. 1 hit.
SSF54680. SSF54680. 1 hit.
TIGRFAMsiTIGR02644. Y_phosphoryl. 1 hit.
PROSITEiPS00647. THYMID_PHOSPHORYLASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTYPH_HUMAN
AccessioniPrimary (citable) accession number: P19971
Secondary accession number(s): A8MW15
, H9KVA0, Q13390, Q8WVB7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: June 7, 2005
Last modified: November 2, 2016
This is version 195 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.